C2006/F2402 -- 2007 --Outline of Lecture #21–
Electrical Communication #2
(c) Stuart Firestein,
Columbia University, New York, NY.
Last update 03/31/2005 04:46 PM .
Notes by Chris Kelly
Click here for a version of these notes that includes extensive spaces (if
you like to take notes on the outline in class)
Some links to animations and additional information on neuroscience are
on the study guides for lectures 16 & 18 from 2004. See
lecture 16 & 17 and
lecture 18. If you need a back up text for the material that isn't in
Becker, you might want to try
Kimball's on line text.
I. Action Potential
- Brief Review
- Action potentials are invariant and rapid changes
in membrane potential used for signaling.
- Depolarization (initial)
- Stimulus causes the ligand-gated sodium
channels to open, causing a passive spread of depolarization inside
- Rising phase
- If that depolarization is sufficient (10 to 15
mV more positive), voltage-gated sodium channels at the axon hillock
suddenly open, causing an enormous influx of sodium and the rapid
- This is essentially a positive-feedback cycle:
sodium entering the cell causes it to depolarize. These depolarized
conditions cause more sodium to enter the cell (because
voltage-gated channels open). This depolarizes the cell even more,
making more sodium channels open, and so on.
- Falling Phase
- Two factors contribute to the cell then racing
back down toward negative potential:
- 1) Voltage-gated sodium channels
inactivate after being open for a certain time. So, those
channels that opened, permitting the depolarization, slam shut
and cannot be opened again until the cell has “reset” itself
back to RMP.
- 2) Voltage-gated potassium channels, which
were tripped during the depolarization (around –20 mV), begin to
open. Why did they not open as soon as the voltage hit –20 mV?
They are slow to undergo the proper conformational changes.
- The net effect is that the permeability to
potassium once again far outweighs that to sodium, so the cell
- The potassium permeability is so high, in
fact, that the cell goes closer to EK than during RMP –
it hyperpolarizes. This brief hyperpolarization can be divided into
- Absolute refractory period (negative
- Voltage-gated sodium channels are
still inactivated, and thus cannot be opened by anything.
Since action potentials depend on these channels, no action
potential is possible. Also, even if such an Na influx were
possible, the K current is too high to be overcome.
- Relative refractory period (positive
- Voltage-gated sodium channels begin to
be released from inactivation, making action potential
possible again, though more stimulus than usual is required
since the cell is farther from threshold than usual.
- Recall that there are no appreciable changes in
concentration at any point in this action potential. All that has changed
are the relative permeabilties of potassium and sodium.
- In fact, were you to poison the Na/K pump,
eliminating the cell’s ability to restore those ions to the correct side
of the membrane, the neuron could still fire another 150,000 action
potentials before the concentrations started to become insufficient.
- Notice that there is little room for variety in this
process, which is why action potentials are (1) invariant, and (2)
all-or-nothing. You cannot have half of an action potential.
To review the action potential, try
problem 8-2, A-C, & 8-3 to 8-4.
- So what is the use of all this? An action potential
is worthless if it does not travel somewhere.
- Action potentials are designed for long-distance
signaling, unlike graded changes in potential (i.e. depolarizations that
do not reach threshold and do vary in amplitude, unlike action
- The action potential is propagated along the axon.
- Think of the axon like a fuse: when you light
a fuse, the end heats up the next segment, which flares up and heats
up the following segment, which then flares up. Unlike a piece of
string, a fuse carries the flame all the way down to the other end.
- Where does the action potential begin?
- At the beginning of the axon, where it first
leaves the soma, there is a concentration of voltage-gated sodium
channels. This area is called the initial segment, or axon hillock. The
propagation down the axon begins with these channels opening.
- When these channels open, positive charge enters
the cell and spreads passively down the axon. This positive charge trips
the next voltage-gated sodium channels on the axon, causing a sodium
influx there, which then causes the next channels to open, and so on.
- Why doesn’t the signal go backward?
- Remember the absolute refractory period. The
positive charge will, in fact, passively spread in both directions in
the axon. When it reaches the segment that just fired, however, those
voltage-gated sodium channels will still be inactivated, and thus unable
to fire an AP.
- How can one ensure that the propagation will make
- Axons can be leaky, and concentration of
voltage-gated sodium channels can vary. A situation could arise in which
the positive charge that enters the axon is not able to trip the next
channel in the series. This is overcome in two ways.
- In invertebrates, the axons are wider, and
thus the conductance is greater. So charge is more easily able to
spread, and propagation is ensured.
- In vertebrates, many axons are myelinated.
Myelin is a fatty substance produced by glial cells that can wrap
itself around the axon membrane. This produces an insulating effect,
allowing charge to travel more easily in the axon.
- In the first case, you have reduced the cable
resistance. In the second case, you have increased the membrane
resistance (and thus reduced “leakiness”). Both result in more
conductance down the axon.
- The myelin “sheath” is useless, however, unless
it has gaps.
- Ions clearly cannot pass through myelin. So
having a myelin sheath around the axon would prevent
signaling unless there are gaps in the myelin dotted along the axon.
These are known as the nodes of Ranvier.
- At each node, there is a high concentration of
sodium and potassium channels. So when the positive charge reaches
the node, the series of electrical events described by the action
potential will occur there. The signal is regenerated. This kind of
signaling is called saltatory conduction, since it appears the
action potential is “jumping” from one node to the next.
- Since action potentials take some time, having
the myelin sheath accelerates the signaling process by reducing the
number of action potential events along the axon. So signaling in
myelinated axons is faster than in unmyelinated axons.
- Conduction velocity can be up to 10 m/s.
- There are several demyelinating diseases in
the nervous system. Multiple sclerosis (MS) is a famous one, in
which an inappropriate autoimmune response results in the
destruction of myelin, thereby interrupting signaling in nerves. One
can see these diseases in images of the nervous system because the
characteristic white color of the myelin is missing in certain
- Note on terminology: even though the cell is
firing action potentials all along its axon, we say that it has
fired a single action potential and simply propagated it.
To review propagation, try problem 8-2 D-E
- So the action potential travels down the axon ––
- The end of the axon is a specialized area with
characteristic proteins and biochemical processes. It is essentially
independent from the soma, even though it gets its material from there.
- This terminal area links one neuron to another,
enabling intercellular communication. These areas of contact are called
synapses, and you have about 1014 of them in your brain ––
three orders of magnitude more than neurons.
- What is the nature of the synapse?
- The big question is whether the link is an
electrical or chemical one.
- Otto Loewi showed that these links are primarily
chemical by placing two frog hearts in bath solution, innervating only
one of them, and then observing that both hearts are affected. In that
particular case, the chemical was acetylcholine, and it was causing the
hearts to slow down their beating. There was no electrical connection
between the hearts, just a chemical one (the solution in which they were
- There are some electrical synapses in the
body; they are created by gap junctions. The myocytes in the heart, for
example, are connected by electrical synapses so that they can
depolarize as a unit, giving a unified heartbeat.
- What is the structure of the synapse?
- The presynaptic neuron is that which fired the
action potential along its axon, to the axonal terminal. The
postsynaptic neuron is the one that its axon contacts.
- There is a space between the two cells known as
the synaptic cleft. It is typically very narrow –– 20 to 40 nm –– but a
- The major players:
- Presynaptic side: calcium and vesicles full of
- Postsynaptic side: neurotransmitter receptors
- The process:
- The action potential races down the axon and
depolarizes the terminal. This causes voltage-gated Ca++
channels at the terminal to open. Since the calcium concentration is
5 mM outside the cell and 0.1 µM inside, calcium rushes in. (FYI:
lots of calcium inside the cell is a bad thing. That’s why the
concentrations are the way they are.)
- Calcium influx causes the vesicles full of
neurotransmitter to dock with the presynaptic membrane and then fuse
with it, causing exocytosis of neurotransmitter into the synaptic
- The NT’s diffuse cross the synaptic cleft and
contact receptors on the postsynaptic side.
- What are the kinds of neurotransmitters?
- Many are amino acids: glutamate, GABA (g-amino
butyric acid), glycine are examples.
- There are also amino acid derivatives: serotonin,
dopamine, epinephrine, etc.
- Acetylcholine (ACh) is another.
- What are their overall effects?
- Neurotransmitters are considered excitatory or
inhibitory, based on whether they produce a depolarization or
hyperpolarization (respectively) in the postsynaptic neuron.
- Glutamate is the main excitatory NT in the CNS;
glycine and GABA are the main inhibitory ones in the CNS. ACh is the
primary NT in the PNS.
- How are these electrical effects produced?
- When NT’s cross the cleft, they bind to receptors.
These receptors are of two kinds:
- Ionotropic: these receptors are also ion
channels. When ligand binds, conformational changes in the channel
subunits are induced, resulting in the opening or closing of the
pore. This is a one-to-one effect: the ligand affects only one
- Metabotropic: the receptors are coupled to
G-Proteins, and the cascade is initiated by the binding of ligand.
The produced cascade usually results in the opening/closing of
channels via second messangers. One ligand can thus affect many
channels in this case.
- In both cases, the opening of channels causes the
flow of ions, which has an electrical effect.
- If the net electrical effect is a
hyperpolarization, than the NT has produced an IPSP (inhibitory
post-synaptic potential). Depolarization -> EPSP (excitatory …).
- There are also gaseous neurotransmitters.
- Nitric oxide, NO, is one example. Unlike solid
neurotransmitters, these can freely diffuse from one cell to another.
- NO initiates a cascade that results in guanalyl
cyclase (GC) producing cGMP, whose net effect is vasodilation in many
cases. Viagra inhibits PDE-3 from breaking down cGMP, thereby
maintaining vasodilation and, hence, an erection.
- GC and cGMP are analogous to AC and cAMP, which we
have already studied. The essential difference is just the nucleotide
To review synapses etc., try problems 8-8 A-G &
8-9. (8-10 & 8-11 are also about synapses.)